Research in this section consists of studies on the physical and chemical properties of proteins of biological interest and the roles of ligand binding and protein-protein interactions in enzyme catalysis and regulation. (1) Active-site ligand interactions with dodecameric glutamine synthetase from E. coli have been studied by spectrophotometric, binding, and calorimetric techniques using the diastereoisomers of L-met-S, R-sulfoximine separately and together. Conformational differences between unadenylylated and adenylylated enzyme forms on binding activesite ligands have been detected. (2) Reactivation of glutamine synthetase after auto-inactivation with L-met-S-sulfoximine, ATP, and MN++ (or MG++) has been accomplished. The reactivation of the enzyme is first-order, dependent on the 3rd-4th power of [H+], and coincides with the release/subunit of 2 MN++, L-met-S-sulfoximine-P, and ADP; increasing the pH from less than or equal to 5 to greater than 6 produces reinactivation. Inter- and intra-subunit bonding domains are markedly stabilized in the inactive enzyme complex. Submolecular, partially active and partially liganded oligomers containing 4,6,8, and 10 subunits have been isolated. (3) Equilibrium and kinetic studies of ME++-protein interactions (using chromogenic chelators and pH indicator dyes) have provided information on the structural and catalytic roles of ME++.